- Therapies that directly modulate brain activity in specific neural networks might be particularly suited to relieve chronic pain in individuals with FM. Ultimately, this underlies the interest in neurostimulation approaches, which are being explored at multiple levels of the neuroaxis, including the peripheral nerves, spinal cord, deep brain structures, and cortex.(Lefaucheur, 2004) Among the methods of central neurostimulation, two of them, repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are particularly appealing as they can change brain activity in a non-invasive, painless and safe way. TMS is a method of brain stimulation that was developed in 1985 (Barker et al., 1985). It is based on a time-varying magnetic field that generates an electric current inside the skull where it can be focused and restricted to small brain areas by appropriate stimulation coil geometry and size.(Pascual-Leone et al., 1999). This current, if applied repetitively, repetitive TMS (rTMS), induces a cortical modulation that lasts beyond the time of stimulation.(Pascual-Leone et al., 1999) Although tDCS has different mechanisms of action, it induces similar modulatory effects. Several animal studies in the 1960s showed that this technique changes brain activity reliably (Nitsche et al., 2003a, 2003b). tDCS is based on the application of a weak direct current to the scalp that flows between two relatively large electrodes—anode and cathode. Some studies have shown that the efficacy of tDCS depends critically on parameters such as electrode position and current strength.(Nitsche et al., 2003a, 2003b) In fact, application of tDCS for 13 min to the motor cortex can modulate cortical excitability for several hours.(Nitsche and Paulus, 2000; Nitsche and Paulus, 2001) In addition, this technique can be used to obtain clinical gains in neuropsychiatric disorders such as stroke and epilepsy.(Fregni and Pascual-Leone, 2007) In this study we will investigate the modulatory effect of 5 daily tDCS sessions on biochemical, functional, and structural systems and its association with the clinical output in FM.